Abbreviations
ABVD: adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine
ADA: adenosine deaminase
ALL: acute lymphoblastic leukemia
AML: acute myeloid leukemia; acute myelocytic leukemia
APL: acute promyelocytic leukemia
Ara-C: cytarabine, cytosine arabinoside
Ara-U: ara-uridine
L-ASP: L-asparaginase
ATO: arsenic trioxide
ATRA: all-trans retinoic acid
AUC: area under the curve
BCNU: carmustine [1,3-bis-(2-chloroethyl)-1-nitrosourea]
BCRP: breast cancer resistance protein
CCNU: 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (lomustine)
CDK: cyclin-dependent kinase
CHOP: cyclophosphamide, doxorubicin (H), vincristine (O), and prednisone
CLCr: creatinine clearance
CLL: chronic lymphocytic leukemia
CML: chronic myelocytic leukemia; chronic myelogenous leukemia
CSF: cerebrospinal fluid
CTCL: cutaneous T-cell lymphoma
dCK: deoxycytidine kinase
dFdC: 2′,2′-difluorodeoxycytidine, gemcitabine
5′-dFdU: 5′-deoxyfluorodeoxyuridine
DHFR: dihydrofolate reductase
DPD: dihydropyrimidine dehydrogenase
FdUMP: fluorodeoxyuridine monophosphate
FOLFIRINOX: FOLFOX plus irinotecan
FOLFOX: folinic acid, 5FU and oxaliplatin
5FU: 5-fluorouracil
FUdR: fluorodeoxyuridine or floxuridine or 5-FUdR
GART: glycinamide ribonucleotide transformylase
G-CSF: granulocyte colony-stimulating factor
HbF: hemoglobin (fetal)
HDM-L: high-dose MTX with leucovorin rescue
HGPRT: hypoxanthine guanine phosphoribosyl transferase
HMG: high-mobility group
HRD: homologous recombination DNA repair
HU: hydroxyurea
IMP: inosine monophosphate
MESNA: 2-mercaptoethanesulfonate-Na+
MGMT: O6-alkyl, methyl guanine methyltransferase
MMR: mismatch repair
MOPP: nitrogen mustard, oncovin (vincristine), procarbazine, and prednisone
6MP: 6-mercaptopurine
MRP: multidrug resistance-associated protein
MTIC: methyl-triazeno-imidazole-carboxamide
MTX: methotrexate
Nab-paclitaxel: albumin-bound nanoparticle solution of paclitaxel
NER: nucleotide excision repair
PG: polyglutamate
Pgp: P-glycoprotein
PML: promyelocytic leukemia
PRPP: 5-phosphoribosyl-1-pyrophosphate
RAR: retinoic acid receptor
RNR: ribonucleoside diphosphate reductase
ROS: reactive oxygen species
TEM: triethylenemelamine
TEPA: triethylenephosphoramide
6TG: 6-thioguanine
Thiotepa: triethylenethiophosphoramide
TPMT: thiopurine methyltransferase
TS: thymidylate synthase
TTP: thymidine triphosphate
VOD: veno-occlusive disease
A Note on Treatment Regimens
Cancer treatment regimens change to reflect continuous advances in basic and clinical science: new drugs, both small molecules and biologicals; improved methods of targeting and timing of drug delivery; agents with altered pharmacokinetic properties and selectivities; the use of rational multidrug combinations; and greater knowledge of the basic cell biology of tumorigenesis, metastasis, and immune function, among other advances. As a consequence, this chapter presents relatively few detailed treatment regimens; rather, we refer the reader to the web-based resources of the U.S. FDA and the National Comprehensive Cancer Network (NCCN.org). Table 71–1 provides two examples of therapeutic regimens that illustrate the complexity of current cancer drug therapy.
HISTORY OF ALKYLATING ANTICANCER DRUGS
The discovery and initial development of alkylating anticancer drugs are based on observations of the effects of chemical warfare in World War I (Chabner and Roberts, 2005). The pervasively toxic sulfur mustard gas that caused topical burns to skin, eyes, lungs, and mucosa also caused aplasia of the bone marrow and lymphoid tissue and ulceration of the GI tract (Krumbhaar, 1919). In 1942, Louis Goodman and Alfred Gilman, the originators of this text, demonstrated the ...